This invention relates to substituted acenaphthenes, and processes for their preparation, pharmaceutical compositions containing them and pharmaceutical methods using them. These compounds have shown activity as inhibitors of the enzyme phospholipase A.sub.2.
The important role of phospholipase A.sub.2 in the biosynthesis of prostaglandins and leukotrienes indicates that inhibitors of phospholipase A.sub.2 may be valuable therapeutic agents having wide applicability in inflammatory and/or allergic conditions in mammals. Although some currently-available anti-inflammatory agents show activity against phospholipase A.sub.2 or other enzymes of the "arachidonic acid cascade," there is a continuing need for safer and more effective drugs capable of treating inflammatory and/or allergic diseases.
W. R. N. Williamson in U.S. Pat. No. 4,246,281 issued Jan. 20, 1981 discloses acenaphthenes of the formula: ##STR3## where Ph represents phenyl optionally substituted by halogen and R.sup.1 represents hydrogen or C.sub.1 -C.sub.4 alkyl. These compounds are useful anti-inflammatory agents.
S. D. Levine in U.S. Pat. No. 3,755,442, issued Aug. 28, 1973, discloses anti-inflammatory acenaphthyl amides and amines having the formula: ##STR4## where R.sup.1 and R.sup.2 may each be hydrogen or a straight or branched chain alkyl radical of up to 6 carbon atoms provided that one R.sup.1 and R.sup.2 is other than hydrogen. Z may be &gt;C.dbd.O or --CH.sub.2 -- and X may be H, halogen, or an alkyl, alkoxy, haloalkyl or haloalkoxy radical of up to 6 carbon atoms.
S. D. Levine and I. T. Harper in U.S. Pat. No. 3,732,299 issued May 8, 1973 disclose anti-inflammatory acenaphthenes of the formula: ##STR5## where at least one of R.sup.1 and R.sup.2 is alkyl and the other may be hydrogen; Z is --CN, --COOR.sup.3 (where R.sup.3 is hydrogen or a hydrocarbon radical or halophenyl), --CH.sub.2 OH, ##STR6## and Y is hydrogen or ##STR7## where R.sup.4 to R.sup.7 are hydrogen or a hydrocarbon radical, A is alkylene, and X is hydrogen, halogen, alkyl, alkoxy, haloalkyl or haloalkoxy.
S. D. Levine in U.S. Pat. No. 3,679,747, issued July 25, 1972, discloses anti-inflammatory acenaphthene derivatives of the formula: ##STR8## where R and R.sup.1 can be the same or different and are C.sub.1 -C.sub.3 alkyl.
C. F. Huebner in U.S. Pat. No. 3,291,830 discloses acenaphthenes of the formula: ##STR9## in which R.sup.1 is a lower 2-alkynyl radical having preferably from 3-5 carbon atoms, R.sup.2 is lower alkyl, the group R.sub.a is a member selected from the group consisting of hydrogen and lower alkyl, and each of the groups R.sub.b and R.sub.c is hydrogen, lower alkyl or halogeno. These compounds are stimulatory agents useful in the treatment of fatigue.
J. F. Kerwin and G. E. Ullyot in U.S. Pat. No. 2,569,814, issued Oct. 2, 1951, disclose acenaphthenes of the formula: ##STR10## in which Z is a member of the group consisting of lower alkyl groups, lower alkenyl groups, phenylalkyl groups, the alkyl portion of which does not exceed 4 carbon atoms, and methoxy-substituted phenylalkyl groups, the alkyl portion of which does not exceed four carbon atoms; R.sub.1 and R.sub.2 are hydrogen or methyl groups; X is chlorine or bromine. These compounds have adrenolytic or sympatholytic properties.